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Celecoxib attenuates hindlimb unloading-induced muscle atrophy via suppressing inflammation, oxidative stress and ER stress by inhibiting STAT3

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Abstract

Improving inflammation may serve as useful therapeutic interventions for the hindlimb unloading-induced disuse muscle atrophy. Celecoxib is a selective non-steroidal anti-inflammatory drug. We aimed to determine the role and mechanism of celecoxib in hindlimb unloading-induced disuse muscle atrophy. Celecoxib significantly attenuated the decrease in soleus muscle mass, hindlimb muscle function and the shift from slow- to fast-twitch muscle fibers caused by hindlimb unloading in rats. Importantly, celecoxib inhibited the increased expression of inflammatory factors, macrophage infiltration in damaged soleus muscle. Mechanistically, Celecoxib could significantly reduce oxidative stress and endoplasmic reticulum stress in soleus muscle of unloaded rats. Furthermore, celecoxib inhibited muscle proteolysis by reducing the levels of MAFbx, MuRF1, and autophagy related proteins maybe by inhibiting the activation of pro-inflammatory STAT3 pathway in vivo and in vitro. This study is the first to demonstrate that celecoxib can attenuate disuse muscle atrophy caused by hindlimb unloading via suppressing inflammation, oxidative stress and endoplasmic reticulum stress probably, improving target muscle function and reversing the shift of muscle fiber types by inhibiting STAT3 pathways-mediated inflammatory cascade. This study not only enriches the potential molecular regulatory mechanisms, but also provides new potential therapeutic targets for disuse muscle atrophy.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China (Nos. 92068112, 82072160, 32130060, 81901933), the Major Natural Science Research Projects in Universities of Jiangsu Province (No. 20KJA310012), the Natural Science Foundation of Jiangsu Province (Nos. BK20202013, BK20201209), the “QingLan Project” in Jiangsu Universities, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Nantong Science and Technology Program (Nos. JC22022037, MS22022010). Nantong university college students’ innovative training program (202310304119Y).

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Author notes

  1. Yanan Ji, Junfei Lin, and Ruiqi Liu have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Medical School of Nantong University, Nantong University, Nantong, Jiangsu Province, 226001, People’s Republic of China

    Yanan Ji, Kexin Wang, Mengyuan Chang, Zihui Gao, Boya Liu, Yuntian Shen, Xinlei Yao & Hualin Sun

  2. Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, People’s Republic of China

    Junfei Lin & Jianwei Zhu

  3. Department of Clinical Medicine, Medical College, Nantong University, Nantong, 226001, China

    Ruiqi Liu

  4. Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, People’s Republic of China

    Lei Qi

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  1. Yanan Ji
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Contributions

Conceptualization, X.Y., L.Q. and H.S.; data curation, Y.J., J.L., R.L., K.W. and M.C.; formal analysis, Y.J., R.L., J.L., B.L. and Z.G.; funding acquisition, Y.S. and H.S.; investigation, Y.J., J.L., R.L., K.W. and M.C.; project administration, X.Y. and H.S.; resources, H.S.; supervision, H.S.; writing—original draft, Y.J., J.L., R.L., K.W. and M.C.; writing—review and editing, Y.S., J.Z., X.Y., L.Q. and H.S. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Xinlei Yao, Lei Qi or Hualin Sun.

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All animal experiments were performed according to the animal care guidelines of Nantong University and were approved by the Jiangsu Provincial Laboratory Animal Management Committee (No. S20200312-003).

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Ji, Y., Lin, J., Liu, R. et al. Celecoxib attenuates hindlimb unloading-induced muscle atrophy via suppressing inflammation, oxidative stress and ER stress by inhibiting STAT3. Inflammopharmacol 32, 1633–1646 (2024). https://doi.org/10.1007/s10787-024-01454-7

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